Although no single variant reached genome-wide significance, an association signal was observed for PNPLA3 rs738409 (p = .01, OR 1.9, 95% CI 1.1-3.1), a common single nucleotide polymorphism that has been associated with a variety of liver-related pathologies including alcoholic cirrhosis.
The absence of an association of PNPLA3 p.I148M with alcoholic CP seems not to point to a common pathway in the development of alcoholic CP and alcoholic liver cirrhosis.
The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.
We found that rs738409 in PNPLA3 is strongly associated with alcoholic liver disease and clinically evident alcoholic cirrhosis (unadjusted OR= 2.25, P=1.7 x 10(-10); ancestry-adjusted OR=1.79, P=1.9 x 10(-5)).